19-46660910-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_145056.3(DACT3):āc.155T>Cā(p.Met52Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000268 in 1,494,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000067 ( 0 hom., cov: 32)
Exomes š: 0.0000022 ( 0 hom. )
Consequence
DACT3
NM_145056.3 missense
NM_145056.3 missense
Scores
1
3
15
Clinical Significance
Conservation
PhyloP100: 0.944
Genes affected
DACT3 (HGNC:30745): (dishevelled binding antagonist of beta catenin 3) Predicted to enable delta-catenin binding activity; protein kinase A binding activity; and protein kinase C binding activity. Involved in negative regulation of canonical Wnt signaling pathway and negative regulation of cell growth. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.068185896).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DACT3 | NM_145056.3 | c.155T>C | p.Met52Thr | missense_variant | 1/4 | ENST00000391916.7 | NP_659493.2 | |
DACT3-AS1 | NR_040042.1 | n.45+502A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DACT3 | ENST00000391916.7 | c.155T>C | p.Met52Thr | missense_variant | 1/4 | 5 | NM_145056.3 | ENSP00000375783 | P1 | |
DACT3 | ENST00000410105.2 | c.155T>C | p.Met52Thr | missense_variant | 1/3 | 2 | ENSP00000387300 | |||
DACT3-AS1 | ENST00000525008.5 | n.45+502A>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000667 AC: 1AN: 149820Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000227 AC: 3AN: 131924Hom.: 0 AF XY: 0.0000138 AC XY: 1AN XY: 72274
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GnomAD4 exome AF: 0.00000223 AC: 3AN: 1344324Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 663978
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GnomAD4 genome AF: 0.00000667 AC: 1AN: 149820Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 73116
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 09, 2023 | The c.155T>C (p.M52T) alteration is located in exon 1 (coding exon 1) of the DACT3 gene. This alteration results from a T to C substitution at nucleotide position 155, causing the methionine (M) at amino acid position 52 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
N;N
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;D
Sift4G
Benign
T;D
Polyphen
P;B
Vest4
MutPred
Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);
MVP
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at